Enantioselective copper-catalyzed conjugate addition to α,β-unsaturated enones using chiral β-silyl amidocuprates

ORGN 463

Abhinav Rastogi1, Craig A. Ogle1, and Steven H. Bertz2. (1) Department of Chemistry, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223-0001, (2) Complexity Study Center, Mendham, NJ 07945

β-silyl groups have been shown to have a pronounced effect on organocuprate reagents. The high reactivity and thermal stability of these reagents have led to their use as non-transferable ligands in Michael addition reactions. We have synthesized and used the first chiral β-silyl amidocuprate for 1,4-conjugate addition to enones. A highly reactive chiral β-silyl amidocuprate has been synthesized from (1R,2S)-(-)-norephedrine. The stoichiometric approach with this chiral auxiliary has been successful, with enantioselectivities reaching > 99%. One advantage of this chiral auxiliary is that the enantioselectivity can be enhanced by conveniently changing the silyl group. These results led us to the copper-catalyzed approach towards these reactions and we have observed enantioselectivity with butyllithium, using chalcone as substrate. The enantioselectivities of this copper-catalyzed conjugate addition with different organolithium reagents, Grignard reagents and dialkylzinc reagents will be discussed.

Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic 9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster Division of Organic Chemistry The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004